Orai1 is required for Ca2+-dependent plasma membrane repair and mechanoadaptation
Luan, H.; Cerci, A.; Bielecki, T. A.; Mohapatra, B. C.; Shrestha, S.; Wu, W.; Storck, M. D.; Smith, L. M.; Stauderman, K. A.; Coulter, D. W.; Kotwal, A.; Dong, J.; Lim, J. Y.; Band, V.; Ramanathan, S. P.; Band, H.
Show abstract
Ca2+-dependent repair of plasma membrane breaches is essential for animal cell viability. An initial passive influx of extracellular Ca2+ triggers the formation of a protein plug that rapidly seals breaches. However, the mechanism of extracellular Ca2+ requirement for subsequent repair remains undefined. EHD2 protein stabilizes the plasma membrane caveolae, which sustain membrane repair, and maintains high surface levels of the caveolae-resident Ca2+ channel Orai1. We establish the requirement of both Orai1 and EHD2 for repair of plasma membrane lesions induced by mechanical injury or by a model bacterial pore-forming toxin. We demonstrate rapid EHD2 recruitment and Orai1-mediated Ca2+ entry at plasma membrane sites of localized mechanical stimulus, the latter requiring EHD2 and CAV1. EHD2 and Orai1 are necessary for mechanosensitive YAP/TAZ-TEAD activation and positive feedback for CAV1 expression that promotes membrane repair. Our studies establish EHD2 and Orai1 as novel components of mammalian plasma membrane repair and mechanoadaptation.
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